To kick off July, 4D Molecular Therapeutics (4DMT) disclosed several key workforce and clinical program updates regarding its phase 3 gene therapy program for wet age-related macular degeneration (AMD).
Most prominent among these announcements: a 25% workforce reduction.
Where do we start with this?
Let’s begin with one of the company’s five candidates: 4D-150, currently under evaluation for both wet AMD and diabetic macular edema (DME).
- But to understand the mechanics of this gene therapy candidate, we need a rundown on 4DMT’s science.
Which brings us to: Therapeutic Vector Evolution, a proprietary vector discovery platform that uses synthetic adeno-associated virus (AAV) capsid-derived sequences to create customized vectors.
- In turn, these customized vectors are used to clinically advance 4DMT’s portfolio of vector delivery-based product candidates—such as the R100 intravitreal (IVT) vector.
How does this relate back to 4D-150?
4D-150 uses the R100 IVT vector, which, in turn, leverages a multi-target transgene payload expressing both aflibercept and a vascular endothelial growth factor (VEGF)-C inhibitory RNA interference (RNAi).
- From there, this dual payload of aflibercept and VEGF-C inhibitory RNAi is intended to block four angiogenic factors that cause wet AMD and DME.
In other words: As a potential “backbone therapy,” 4D-150 induces continuous expression of two therapeutic transgenes from retinal cells to suppress those four different VEGF family members at the location of disease (either wet AMD or DME) activity.
And how is this treatment delivered?
Via a single, low-dose, and sustained, mult-year IVT injection.
Now to its clinical program.
Take note: 4D-150 has already demonstrated a superior reduction in supplemental anti-VEGF injections and mean central subfield thickness (CST) and resulted in positive visual outcomes in its phase 2 clinical findings.
- Read up on that 52-week data, reported in February 2025.
As for this phase 3 4FRONT global registrational clinical program: The company announced plans to accelerate the timeline for the planned 4FRONT clinical trials to enable an anticipated Biologics License Application (BLA) submission for 4D-150’s wet AMD indication.
Those trials include:
- 4FRONT-1
- About this: Conducted in North America, 4DMT reported that initial enrollment and site activation have “exceeded projections”
- Timeframe: 52-week topline data expected in H1 2027 (earlier than the original H2 2027 timeline)
- About this: Conducted in North America, 4DMT reported that initial enrollment and site activation have “exceeded projections”
- 4FRONT-2
- About this: Initiated in June 2025 (ahead of schedule) and identical in design to 4FRONT-1 (save for enrolling both treatment-naïve and recently diagnosed, treatment-experienced patients)
- Timeframe: 52-week topline data expected in H2 2027 (as originally planned)
- About this: Initiated in June 2025 (ahead of schedule) and identical in design to 4FRONT-1 (save for enrolling both treatment-naïve and recently diagnosed, treatment-experienced patients)
What did the company have to say about these updates?
In speaking on 4D-150’s clinical progress, 4DMT Chief Development Officer Dhaval Desai stated that these latest advancements “confirm our belief that durable treatment burden is the greatest unmet need for (wet AMD) patients.”
Next: The elephant in the room (those workforce cuts).
As of this month, the 4DMT laid off around 25% of its staff—largely in the early-stage research and development (R&D) areas.
- To put this in actual numbers: That equates to around 57 individuals.
- That’s based on the company’s reported headcount of 227 full-time employees (of which 166 were in R&D) in February 2025
And how much is this saving the company?
An estimated $15 million in annual savings.
- Take note: 4DMT estimated it will pay around $3 million in cash expenses (to cover severance, benefits, and related termination costs)
So what’s the reasoning behind this?
The company shared that this cost savings will be used to offset anticipated additional expenses it incurred as a result of the 4FRONT phase 3 program’s accelerated timeline and BLA submission preparations.
And with these extra funds: 4DMT stated it now has enough in cash supply to support its financial target into 2028.
Disregarding that $15M for a moment, how much does 4DMT have in the bank?
As of a July 2 SEC filing, the company reported $458 million in cash, cash equivalents, and marketable securities—an amount that “is sufficient to support planned expenses” for the company’s upcoming plans, including:
- Delivering 52-week topline data from 4FRONT-1 and 4FRONT-2 phase 3 clinical trials
- BLA preparations for 4D-150 in wet AMD
- Continuing phase 1/2 and pre-phase 3 planning activities for 4D-150 in DME
- Furthering ongoing phase 1/2 development of 4D-710 (another candidate) for cystic fibrosis
And, remind me—what’s next for 4DMT?
With this streamlined planning underway, stay tuned for a data readout from the 4FRONT-1 phase 3 trial in H2 2027 (and likely clinical progress updates in the meantime).